For Consumers

What are the possible side effects of panitumumab (Vectibix)?

Some people receiving a panitumumab injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, nauseated, light-headed, sweaty, itchy, or have a fever, chills, or trouble breathing during the injection.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some of the side effects of panitumumab may not appear when you first start using the medication. Severe skin or eye reactions may...

Limitation Of Use

Vectibix is not indicated for
the treatment of patients with KRAS-mutant mCRC or for whom KRAS mutation
status is unknown [see DOSAGE AND ADMINISTRATION, WARNINGS AND
PRECAUTIONS, and CLINICAL PHARMACOLOGY].

DOSAGE AND ADMINISTRATION

Patient Selection

Prior to initiation of
treatment with Vectibix, assess KRAS mutational status in colorectal tumors and
confirm the absence of a KRAS mutation using an FDA-approved test [see WARNINGS
AND PRECAUTIONS]. Information on FDA-approved tests for the detection of KRAS
mutations in patients with metastatic colorectal cancer is available at:
http://www.fda.gov/CompanionDiagnostics.

Recommended Dose

The recommended dose of
Vectibix is 6 mg/kg, administered as an intravenous infusion over 60 minutes,
every 14 days. If the first infusion is tolerated, administer subsequent
infusions over 30 to 60 minutes. Administer doses higher than 1000 mg over 90
minutes [see Preparation and Administration].

Appropriate medical resources
for the treatment of severe infusion reactions should be available during
Vectibix infusions [see WARNINGS AND PRECAUTIONS].

Dose Modifications for Dermatologic Toxicity

Upon first occurrence of a grade 3 (NCI-CTC/CTCAE)
dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction
improves to < grade 3, reinitiate Vectibix at the original dose.

Upon the second occurrence of a grade 3 (NCI-CTC/CTCAE)
dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction
improves to < grade 3, reinitiate Vectibix at 80% of the original dose.

Upon the third occurrence of a grade 3 (NCI-CTC/CTCAE)
dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction
improves to < grade 3, reinitiate Vectibix at 60% of the original dose.

Permanently discontinue Vectibix following the occurrence
of a grade 4 dermatologic reaction or for a grade 3 (NCI-CTC/CTCAE)
dermatologic reaction that does not recover after withholding 1 or 2 doses.

Preparation And Administration

Do not administer Vectibix as an intravenous push or
bolus.

Preparation

Prepare the solution for infusion, using aseptic
technique, as follows:

Parenteral drug products should be inspected visually for
particulate matter and discoloration prior to administration. Although Vectibix
should be colorless, the solution may contain a small amount of visible
translucent-to-white, amorphous, proteinaceous, panitumumab particulates (which
will be removed by filtration; see below). Do not shake. Do not administer
Vectibix if discoloration is observed.

Withdraw the necessary amount of Vectibix for a dose of 6
mg/kg.

Dilute to a total volume of 100 mL with 0.9% sodium
chloride injection, USP. Doses higher than 1000 mg should be diluted to 150 mL
with 0.9% sodium chloride injection, USP. Do not exceed a final concentration
of 10 mg/mL.

Mix diluted solution by gentle inversion. Do not shake.

Administration

Flush line before and after Vectibix administration with
0.9% sodium chloride injection, USP, to avoid mixing with other drug products
or intravenous solutions. Do not mix Vectibix with, or administer as an
infusion with, other medicinal products. Do not add other medications to
solutions containing panitumumab.

Infuse doses of 1000 mg or lower over 60 minutes through
a peripheral intravenous line or indwelling intravenous catheter. If the first
infusion is tolerated, administer subsequent infusions over 30 to 60 minutes.
Administer doses higher than 1000 mg over 90 minutes.

Use the diluted infusion solution of Vectibix within 6
hours of preparation if stored at room temperature, or within 24 hours of
dilution if stored at 2° to 8°C (36° to 46°F). DO NOT FREEZE.

Store vials in the original
carton under refrigeration at 2° to 8°C (36° to 46°F) until time of use.
Protect from direct sunlight. DO NOT FREEZE. Since Vectibix does not contain
preservatives, any unused portion remaining in the vial must be discarded.

The diluted infusion solution of Vectibix should be used
within 6 hours of preparation if stored at room temperature, or within 24 hours
of dilution if stored at 2° to 8°C (36° to 46°F). DO NOT FREEZE.

Increased Mortality and Toxicity with Vectibix in
combination with Bevacizumab and Chemotherapy [see WARNINGS
AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying
conditions, adverse reaction rates in the clinical trials of a drug cannot be
directly compared to rates in clinical trials of another drug and may not
reflect the rates observed in practice. The adverse reaction information from
clinical studies does, however, provide a basis for identifying the adverse
events that appear to be related to drug use and for approximating rates.

Vectibix Monotherapy

In Study 1, the most common adverse reactions ( ≥
20%) with Vectibix were skin rash with variable presentations, paronychia,
fatigue, nausea, and diarrhea.

The most common ( > 5%) serious adverse reactions in
the Vectibix arm were general physical health deterioration and intestinal
obstruction. The most frequently reported adverse reactions for Vectibix
leading to withdrawal were general physical health deterioration (n = 2) and
intestinal obstruction (n = 2).

For Study 1, the data described in Table 1 and in other
sections below, except where noted, reflect exposure to Vectibix administered
to patients with mCRC as a single agent at the recommended dose and schedule (6
mg/kg every 2 weeks).

In Study 1, dermatologic
toxicities occurred in 90% of patients receiving Vectibix. Skin toxicity was
severe (NCICTC grade 3 and higher) in 15% of patients. Ocular toxicities
occurred in 16% of patients and included, but were not limited to,
conjunctivitis (5%). One patient experienced an NCI-CTC grade 3 event of
mucosal inflammation. The incidence of paronychia was 25% and was severe in 2%
of patients [see WARNINGS AND PRECAUTIONS].

In Study 1 (N = 229), median
time to the development of dermatologic, nail, or ocular toxicity was 12 days
after the first dose of Vectibix; the median time to most severe skin/ocular
toxicity was 15 days after the first dose of Vectibix; and the median time to
resolution after the last dose of Vectibix was 98 days. Severe toxicity
necessitated dose interruption in 11% of Vectibix-treated patients [see DOSAGE
AND ADMINISTRATION].

Subsequent to the development of severe dermatologic
toxicities, infectious complications, including sepsis, septic death,
necrotizing fasciitis, and abscesses requiring incisions and drainage were
reported.

Infusion Reactions

Infusional toxicity manifesting
as fever, chills, dyspnea, bronchospasm or hypotension was assessed within 24
hours of an infusion during the clinical study. Vital signs and temperature
were measured within 30 minutes prior to initiation and upon completion
of the Vectibix infusion. The use of premedication was not standardized in the
clinical trials. Thus, the utility of premedication in preventing the first or
subsequent episodes of infusional toxicity is unknown. Across clinical trials
of Vectibix monotherapy, 3% (24/725) experienced infusion reactions of which
< 1% (3/725) were severe (NCI-CTC grade 3-4). In one patient, Vectibix was
permanently discontinued for a serious infusion reaction [see DOSAGE AND
ADMINISTRATION].

Immunogenicity

As with all therapeutic proteins, there is potential for
immunogenicity. The immunogenicity of Vectibix has been evaluated using two
different screening immunoassays for the detection of binding anti-panitumumab
antibodies: an acid dissociation bridging enzyme-linked immunosorbent assay
(ELISA) detecting high-affinity antibodies and a Biacore® biosensor
immunoassay detecting both high-and low-affinity antibodies. For patients whose
sera tested positive in screening immunoassays, an in vitro biological assay
was performed to detect neutralizing antibodies.

Monotherapy

The incidence of binding anti-panitumumab antibodies
(excluding preexisting and transient positive patients) was 0.4% (5/1123) as
detected by the acid dissociation ELISA and 3.2% (36/1123) as detected by the
Biacore® assay. The incidence of neutralizing anti-panitumumab
antibodies (excluding preexisting and transient positive patients) was 0.8%
(9/1123). There was no evidence of altered pharmacokinetic or safety profiles
in patients who developed antibodies to Vectibix.

In combination with chemotherapy: The incidence of
binding anti-panitumumab antibodies (excluding preexisting positive patients)
was 0.9% (12/1297) as detected by the acid dissociation ELISA and 0.7% (9/1296)
as detected by the Biacore® assay. The incidence of neutralizing
anti-panitumumab antibodies (excluding preexisting positive patients) was 0.2%
(2/1297). No evidence of an altered safety profile was found in patients who
developed antibodies to Vectibix.

The detection of antibody formation is highly dependent
on the sensitivity and specificity of the assay. Additionally, the observed
incidence of antibody (including neutralizing antibody) positivity in an assay
may be influenced by several factors, including assay methodology, sample
handling, timing of sample collection, concomitant medications, and underlying
disease. For these reasons, comparison of the incidence of antibodies to
panitumumab with the incidence of antibodies to other products may be
misleading.

Postmarketing Experience

The following adverse reactions have been identified
during post-approval use of Vectibix. Because these reactions are reported in a
population of uncertain size, it is not always possible to reliably estimate
their frequency or establish a causal relationship to drug exposure.

Monitor patients who develop dermatologic or soft tissue
toxicities while receiving Vectibix for the development of inflammatory or
infectious sequelae. Life-threatening and fatal infectious complications
including necrotizing fasciitis, abscesses, and sepsis have been observed in
patients treated with Vectibix. Life-threatening and fatal bullous
mucocutaneous skin disease has also been observed in patients treated with
Vectibix. Withhold or discontinue Vectibix for dermatologic or soft tissue
toxicity associated with severe or life-threatening inflammatory or infectious
complications [see BOXED WARNING and ADVERSE REACTIONS]. Dose
modifications for Vectibix concerning dermatologic toxicity are provided [seeDOSAGE AND ADMINISTRATION].

Determination of KRAS mutational status in colorectal
tumors using an FDA-approved test indicated for this use is necessary for
selection of patients for treatment with Vectibix. Vectibix is indicated only
for the treatment of patients with KRAS wild-type mCRC. Vectibix is not
indicated for the treatment of patients with colorectal cancer that harbor
somatic mutations in codons 12 and 13 (exon 2) as determined by an FDA-approved
test for this use [seeINDICATIONS AND USAGE, DOSAGE AND
ADMINISTRATION, CLINICAL PHARMACOLOGY and Clinical Studies].
In Study 3, 221 patients with KRAS-mutant mCRC tumors receiving Vectibix in
combination with FOLFOX experienced shorter overall survival (OS) compared to
219 patients receiving FOLFOX alone (HR = 1.24, 95% CI: 0.98-1.57). Perform the
assessment for KRAS mutational status in colorectal cancer in laboratories with
demonstrated proficiency in the specific technology being utilized. Improper
assay performance can lead to unreliable test results. Refer to an FDA-approved
test's package insert for instructions on the identification of patients
eligible for the treatment of Vectibix.

Electrolyte Depletion/Monitoring

Progressively decreasing serum magnesium levels leading
to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 2) of
patients across clinical trials. Monitor patients for hypomagnesemia and
hypocalcemia prior to initiating Vectibix treatment, periodically during
Vectibix treatment, and for up to 8 weeks after the completion of treatment.
Other electrolyte disturbances, including hypokalemia, have also been observed.
Replete magnesium and other electrolytes as appropriate.

Acute Renal Failure In Combination With Chemotherapy

Severe diarrhea and dehydration, leading to acute renal
failure and other complications, have been observed in patients treated with
Vectibix in combination with chemotherapy.

Pulmonary Fibrosis/Interstitial Lung Disease (ILD)

Fatal and nonfatal cases of interstitial lung disease
(ILD) (1%) and pulmonary fibrosis have been observed in patients treated with
Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients
enrolled in clinical studies of Vectibix. In the event of acute onset or
worsening of pulmonary symptoms, interrupt Vectibix therapy. Discontinue
Vectibix therapy if ILD is confirmed.

In patients with a history of interstitial pneumonitis or
pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary
fibrosis, the benefits of therapy with Vectibix versus the risk of pulmonary
complications must be carefully considered.

Photosensitivity

Ocular Toxicities

Keratitis and ulcerative keratitis, known risk factors
for corneal perforation, have been reported with Vectibix use. Monitor for
evidence of keratitis or ulcerative keratitis. Interrupt or discontinue
Vectibix therapy for acute or worsening keratitis.

Increased Mortality And Toxicity With Vectibix In Combination
With Bevacizumab And Chemotherapy

As a result of the toxicities experienced, patients
randomized to Vectibix, bevacizumab, and chemotherapy received a lower mean
relative dose intensity of each chemotherapeutic agent (oxaliplatin,
irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on
study compared with those randomized to bevacizumab and chemotherapy.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No carcinogenicity or mutagenicity studies of panitumumab
have been conducted. It is not known if panitumumab can impair fertility in
humans. Prolonged menstrual cycles and/or amenorrhea occurred in normally
cycling, female cynomolgus monkeys treated weekly with 1.25 to 5 times the
recommended human dose of panitumumab (based on body weight). Menstrual cycle
irregularities in panitumumab-treated female monkeys were accompanied by both a
decrease and delay in peak progesterone and 17β-estradiol levels. Normal
menstrual cycling resumed in most animals after discontinuation of panitumumab
treatment. A no-effect level for menstrual cycle irregularities and serum
hormone levels was not identified. The effects of panitumumab on male fertility
have not been studied. However, no adverse effects were observed
microscopically in reproductive organs from male cynomolgus monkeys treated for
26 weeks with panitumumab at doses of up to approximately 5-fold the
recommended human dose (based on body weight).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no studies of Vectibix in pregnant women.
Reproduction studies in cynomolgus monkeys treated with 1.25 to 5 times the
recommended human dose of panitumumab resulted in significant embryolethality
and abortions; however, no other evidence of teratogenesis was noted in
offspring [see Nonclinical Toxicology]. Vectibix should be used during
pregnancy only if the potential benefit justifies the potential risk to the
fetus.

Based on animal models, EGFR is involved in prenatal
development and may be essential for normal organogenesis, proliferation, and
differentiation in the developing embryo. Human IgG is known to cross the
placental barrier; therefore, panitumumab may be transmitted from the mother to
the developing fetus, and has the potential to cause fetal harm when
administered to pregnant women.

Women who become pregnant during Vectibix treatment are
encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or
their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

Nursing Mothers

It is not known whether panitumumab is excreted into
human milk; however, human IgG is excreted into human milk. Published data
suggest that breast milk antibodies do not enter the neonatal and infant
circulation in substantial amounts. Because many drugs are excreted into human
milk and because of the potential for serious adverse reactions in nursing
infants from Vectibix, a decision should be made whether to discontinue nursing
or to discontinue the drug, taking into account the importance of the drug to
the mother. If nursing is interrupted, based on the mean half-life of
panitumumab, nursing should not be resumed earlier than 2 months following the
last dose of Vectibix [seeCLINICAL PHARMACOLOGY].

Women who are nursing during Vectibix treatment are
encouraged to enroll in Amgen's Lactation Surveillance Program. Patients or
their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

Pediatric Use

The safety and effectiveness of Vectibix have not been
established in pediatric patients. The pharmacokinetic profile of Vectibix has
not been studied in pediatric patients.

Geriatric Use

Of the 737 patients who received Vectibix monotherapy in
Study 1 and 2, 36% were 65 and over while 8% were 75 and over. No overall
differences in safety or efficacy were observed in elderly patients ( ≥ 65
years of age) treated with Vectibix monotherapy.

Of the 322 patients in Study 3 who received Vectibix plus
FOLFOX, 128 (40%) were 65 and over while 8% were 75 and over. Patients older
than 65 years of age experienced an increased incidence of serious adverse
events (52% vs 36%) and an increased incidence of serious diarrhea (15% vs 5%)
as compared to younger patients.

CONTRAINDICATIONS

CLINICAL PHARMACOLOGY

Mechanism Of Action

The EGFR is a transmembrane glycoprotein that is a member
of a subfamily of type I receptor tyrosine kinases, including EGFR, HER2, HER3,
and HER4. EGFR is constitutively expressed in normal epithelial tissues,
including the skin and hair follicle. EGFR is overexpressed in certain human
cancers, including colon and rectum cancers. Interaction of EGFR with its
normal ligands (eg, EGF, transforming growth factor-alpha) leads to
phosphorylation and activation of a series of intracellular proteins, which in turn
regulate transcription of genes involved with cellular growth and survival,
motility, and proliferation. Signal transduction through the EGFR results in
activation of the wild-type KRAS protein. However, in cells with activating KRAS
somatic mutations, the KRAS-mutant protein is continuously active and appears
independent of EGFR regulation.

Panitumumab binds specifically to EGFR on both normal and
tumor cells, and competitively inhibits the binding of ligands for EGFR.
Nonclinical studies show that binding of panitumumab to the EGFR prevents
ligand-induced receptor autophosphorylation and activation of
receptor-associated kinases, resulting in inhibition of cell growth, induction
of apoptosis, decreased proinflammatorycytokine and vascular growth factor
production, and internalization of the EGFR. In vitro assays and in vivo animal
studies demonstrate that panitumumab inhibits the growth and survival of
selected human tumor cell lines expressing EGFR.

Pharmacokinetics

Panitumumab administered as a single agent exhibits
nonlinear pharmacokinetics.

Following single-dose administrations of panitumumab as
1-hour infusions, the area under the concentration-time curve (AUC) increased
in a greater than dose-proportional manner, and clearance (CL) of panitumumab
decreased from 30.6 to 4.6 mL/day/kg as the dose increased from 0.75 to 9
mg/kg. However, at doses above 2 mg/kg, the AUC of panitumumab increased in an
approximately dose-proportional manner.

Following the recommended dose regimen (6 mg/kg given
once every 2 weeks as a 1-hour infusion), panitumumab concentrations reached
steady-state levels by the third infusion with mean (± SD) peak and trough
concentrations of 213 ± 59 and 39 ± 14 mcg/mL, respectively. The mean (± SD)
AUC0-tau and CL were 1306 ± 374 mcg•day/mL and 4.9 ± 1.4 mL/kg/day,
respectively. The elimination half-life was approximately 7.5 days (range: 3.6
to 10.9 days).

A population pharmacokinetic analysis was performed to
explore the potential effects of selected covariates on panitumumab
pharmacokinetics. Results suggest that age (21-88 years), gender, race (15%
nonwhite), mild-tomoderate renal dysfunction, mild-to-moderate hepatic
dysfunction, and EGFR membrane-staining intensity (1+, 2+, and 3+) in tumor
cells had no apparent impact on the pharmacokinetics of panitumumab.

No formal pharmacokinetic studies of panitumumab have
been conducted in patients with renal or hepatic impairment.

Animal Toxicology And/Or Pharmacology

Weekly administration of panitumumab to cynomolgus
monkeys for 4 to 26 weeks resulted in dermatologic findings, including
dermatitis, pustule formation and exfoliative rash, and deaths secondary to
bacterial infection and sepsis at doses of 1.25 to 5-fold higher (based on body
weight) than the recommended human dose.

Reproductive And Developmental Toxicology

Pregnant cynomolgus monkeys were treated weekly with
panitumumab during the period of organogenesis (gestation day [GD] 20-50).
While no panitumumab was detected in serum of neonates from panitumumab-treated
dams, anti-panitumumab antibody titers were present in 14 of 27 offspring delivered
at GD 100. There were no fetal malformations or other evidence of teratogenesis
noted in the offspring. However, significant increases in embryolethality and
abortions occurred at doses of approximately 1.25 to 5 times the recommended
human dose (based on body weight).

Clinical Studies

Recurrent Or Refractory mCRC

The safety and efficacy of Vectibix was demonstrated in
Study 1, an open-label, multinational, randomized, controlled trial of 463
patients with EGFR-expressing, metastatic carcinoma of the colon or rectum, and
in Study 2, an open-label, multicenter, multinational, randomized trial of 1010
patients with wild-type KRAS mCRC.

Study 1

Patients in Study 1 were required to have progressed on
or following treatment with a regimen(s) containing a fluoropyrimidine,
oxaliplatin, and irinotecan; progression was confirmed by an independent review
committee (IRC) masked to treatment assignment for 76% of the patients.
Patients were randomized (1:1) to receive panitumumab at a dose of 6 mg/kg
given once every 2 weeks plus BSC (N = 231) or BSC alone (N = 232) until
investigator-determined disease progression. Randomization was stratified based
on Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 and 1
vs 2) and geographic region (Western Europe, Eastern/Central Europe, or other).
Upon investigator-determined disease progression, patients in the BSC-alone arm
were eligible to receive panitumumab and were followed until disease
progression was confirmed by the IRC.

Based upon IRC determination of disease progression, a
statistically significant prolongation in PFS was observed in patients
receiving panitumumab compared to those receiving BSC alone. The mean PFS was
96 days in the panitumumab arm and 60 days in the BSC-alone arm.

The study results were analyzed in the wild-type KRAS subgroup
where KRAS status was retrospectively determined using archived
paraffin-embedded tumor tissue. KRAS mutation status was determined in 427
patients (92%); of these, 243 (57%) had no detectable KRAS mutations in either
codons 12 or 13. The hazard ratio for PFS in patients with wild-type KRAS mCRC
was 0.45 (95% CI: 0.34-0.59) favoring the panitumumab arm. The response rate
was 17% for the panitumumab arm and 0% for BSC. There were no differences in
OS; 77% of patients in the BSC arm received panitumumab at the time of disease
progression.

Study 2

Study 2 was an open-label, multicenter, multinational,
randomized (1:1) clinical trial, stratified by region (North America, Western
Europe, and Australia versus rest of the world) and ECOG PS (0 and 1 vs 2) in
patients with wild-type KRAS mCRC. A total of 1010 patients who received prior
treatment with irinotecan, oxaliplatin, and a thymidylate synthase inhibitor
were randomized to receive Vectibix 6 mg/kg intravenously over 60 minutes every
14 days or cetuximab 400 mg/m² intravenously over 120 minutes on day
1 followed by 250 mg/m² intravenously over 60 minutes every 7 days.
The trial excluded patients with clinically significant cardiac disease and
interstitial lung disease. The major efficacy analysis tested whether the OS of
Vectibix was noninferior to cetuximab. Data for investigator-assessed PFS and
objective response rate (ORR) were also collected. The criteria for
noninferiority was for Vectibix to retain at least 50% of the OS benefit of
cetuximab based on an OS hazard ratio of 0.55 from the NCIC CTG CO.17 study
relative to BSC.

In Study 2, 37% of patients were women, 52% were white,
45% were Asian, and 1.3% were Hispanic or Latino. Thirty-one percent of
patients were enrolled at sites in North America, Western Europe, or Australia.
ECOG performance was 0 in 32% of patients, 1 in 60% of patients, and 2 in 8% of
patients. Median age was 61 years. More patients (62%) had colon cancer than
rectal cancer (38%). Most patients (74%) had not received prior bevacizumab.

The key efficacy analysis for Study 2 demonstrated that
Vectibix was statistically significantly noninferior to cetuximab for OS.

The efficacy results for Study 2 are presented in Table 3
and Figure 1.

Table 3: Results in Previously Treated Wild-type KRAS mCRC
(Study 2)

Wild-type KRAS Population

Vectibix
(n = 499)a

Cetuximab
(n = 500)a

OS

Number of OS events (%)

383 (76.8)

392 (78.4)

Median (months) (95% CI)

10.4 (9.4, 11.6)

10.0 (9.3, 11.0)

Hazard ratio (95% CI)

0.97 (0.84, 1.11)

PFS

Median (months) (95% CI)

4.1 (3.2, 4.8)

4.4 (3.2, 4.8)

Hazard ratio (95% CI)

1.00 (0.88, 1.14)

ORR

% (95% CI)

22% (18%, 26%)

19% (16%, 23%)

aModified intent-to-treat population that
included all patients who received at least one dose of therapy

First-line in Combination with
FOLFOX Chemotherapy

Study 3

Study 3 was a multicenter,
open-label trial that randomized (1:1) patients with mCRC who were previously
untreated in the metastatic setting and who had received no prior oxaliplatin
to receive Vectibix every 14 days in combination with FOLFOX or to FOLFOX alone
every 14 days. Vectibix was administered at 6 mg/kg over 60 minutes prior to
administration of chemotherapy. The FOLFOX regimen consisted of oxaliplatin 85
mg per m² IV infusion over 120 minutes and leucovorin (dl-racemic)
200 mg per m² intravenous infusion over 120 minutes at the same time
on day 1 using a Y-line, followed on day 1 by 5-FU 400 mg per m² intravenous
bolus. The 5FU bolus was followed by a continuous infusion of 5-FU 600 mg per m² over 22 hours. On day 2, patients received leucovorin 200 mg per m² followed
by the bolus dose (400 mg per m²) and continuous infusion of 5FU
(600 mg per m²) over 22 hours. Study 3 excluded patients with known
central nervous system metastases, clinically significant cardiac disease,
interstitial lung disease, or active inflammatory bowel disease. The prespecified
major efficacy measure was PFS in patients (n = 656) with wild-type KRAS mCRC
as assessed by a blinded independent central review of imaging. Other key
efficacy measures included OS and ORR.

In Study 3, in the wild-type KRAS
group, 64% of patients were men, 92% white, 2% black, and 4% Hispanic or
Latino. Sixty-six percent of patients had colon cancer and 34% had rectal
cancer. ECOG performance was 0 in 56% of patients, 1 in 38% of patients, and 2
in 6% of patients. Median age was 61.5 years.

The efficacy results in Study 3
in patients with wild-type KRAS mCRC are presented in Table 4 below.